Abstract
The fidelity of replication is regulated by the DNA damage response (DDR), an elaborate signaling network of proteins that detect, signal, and repair DNA lesions. While some viruses have evolved mechanisms to avoid or eliminate DNA repair machinery, others exploit the DDR to replicate their genomes [1]. Recent studies indicate that the DDR facilitates productive replication of human papillomaviruses (HPV) [2–8]. The ability of cells to detect and repair DNA breaks is dependent on the reorganization of surrounding chromatin [9]. The importance of histone post-translational modifications and chromatin remodeling proteins in recruitment of repair factors to DNA breaks is becoming increasingly clear. HPV genomes are histone-associated in the virion and exhibit a nucleosome pattern similar to that of cellular DNA in infected cells [10,11]. HPV chromatin is subject to histone modifications, likely important in ensuring the correct temporal expression of viral genes through the life cycle [12,13]. However, the assembly of DNA repair factors in large complexes at HPV replication centers raises the intriguing possibility that viral chromatin may also be subject to the changing chromatin dynamics associated with the DDR, facilitating efficient productive replication through DNA repair mechanisms.
Highlights
The fidelity of replication is regulated by the DNA damage response (DDR), an elaborate signaling network of proteins that detect, signal, and repair DNA lesions
Given that the recruitment of 53BP1 as well as BRCA1 to double-strand breaks (DSBs) can occur in an ubiquitin-dependent manner, these results suggest that Ring Finger 8 (RNF8)/RNF168 may localize to viral DNA
The binding of γH2AX to viral DNA suggests that human papillomaviruses (HPV)-induced activation of ataxia-telangiectasia mutated (ATM) results in chromatin changes that promote the recruitment of homologous recombination (HR) rather than non-homologous end joining (NHEJ) factors to viral replication centers
Summary
The fidelity of replication is regulated by the DNA damage response (DDR), an elaborate signaling network of proteins that detect, signal, and repair DNA lesions. The ability of cells to detect and repair DNA breaks is dependent on the reorganization of surrounding chromatin [9]. The importance of histone post-translational modifications and chromatin remodeling proteins in recruitment of repair factors to DNA breaks is becoming increasingly clear. HPV genomes are histone-associated in the virion and exhibit a nucleosome pattern similar to that of cellular DNA in infected cells [10,11]. HPV chromatin is subject to histone modifications, likely important in ensuring the correct temporal expression of viral genes through the life cycle [12,13]. The assembly of DNA repair factors in large complexes at HPV replication centers raises the intriguing possibility that viral chromatin may be subject to the changing chromatin dynamics associated with the DDR, facilitating efficient productive replication through DNA repair mechanisms
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